Neurons are the cells that make up our nervous system, and they're made up of three main parts. The dendrite, which are little branches off the neuron that receive signals from other neurons, the soma or cell body, which has all of the neuron's main organelles like the nucleus, and the axon, which is intermittently wrapped in fatty myelin. Those dendrites receive signals from other neurons via neurotransmitters. which, when they bind to receptors on the dendrite, act as a chemical signal.
That binding opens ion channels that allow charged ions to flow in and out of the cell, converting the chemical signal into an electrical signal. Since a single neuron can have a ton of dendrites receiving input, if the combined effect of multiple dendrites changes the overall charge of the cell enough, then it triggers an action potential, which is an electrical signal that races down the axon up to 100 meters per second. triggering the release of neurotransmitter on the other end, and further relaying the signal.
So neurons use neurotransmitters as a signal to communicate with each other, but they use action potentials to propagate that signal within the cell. Some of these neurons can be very long, especially ones that go from the spinal cord to the toes, so the movement of this electrical signal within the cell is super important. But why does a cell have an electrical charge in the first place? Well it's based on different concentrations of ions on the inside vs the outside of the cell. Generally speaking, there are more Na+, or sodium ions, Cl-or chloride ions, and Ca2 or calcium ions on the outside of the cell, and more K+, or potassium ion, and A-which we just use for negatively charged anions, on the inside of the cell.
Overall, the distribution of these ions gives the cell a net negative charge of close to negative 65 millivolts relative to the outside environment, and this is the neuron's resting membrane potential. When a neurotransmitter binds to a receptor on the dendrite, a ligand-gated ion channel opens up to allow certain ions to flow in, depending on the channel. Ligand-gated literally means that the gate responds to a ligand, which in this case is a neurotransmitter.
So let's take the example of a ligand-gated sodium ion channel, which when it opens lets sodium flow into the cell. The extra positive charge that flows in makes the cell less negative, since remember it's usually negative 65 mV, and therefore less polar, so that's why gaining positive charge is called depolarization. Neurotransmitters typically open various ligand-gated ion channels all at once, so ions like sodium and calcium might flow in.
while other ions like potassium might flow out, which would actually mean some positive charge leaves the cell. In the end though, when it's all added up, if there's a net influx of positive charge, then it's called an excitatory postsynaptic potential, or EPSP. In contrast, the opening of only ligand-gated chloride ion channels would cause a net influx of negative charge, creating an inhibitory postsynaptic potential, or IPSP.
making the cell potential more negative or repolarizing it. Now a single EPSP or IPSP causes only a small change on the resting membrane potential, but if there are enough EPSPs across multiple sites on the dendrites, then collectively they can push the membrane potential to a specific threshold value, typically around negative 55 mV, although this can vary depending on the tissue. When it hits this threshold value, It triggers the opening of voltage-gated sodium channels at the start of the axon, which is called the axon hillock.
These voltage-gated channels open in response to a change in voltage, and when these open, sodium rushes into the cell. The influx of sodium ions and the resulting change in membrane potential causes nearby voltage-gated sodium channels to open as well, setting off this chain reaction that continues down the entire length of the axon, which ends up being our action potential. And when this happens, we say that the neuron has fired.
Once a lot of sodium has rushed across the neuronal membrane, the cell actually becomes positively charged relative to the external environment, up to about positive 40 millivolts. This depolarization process ends when the sodium channel stops allowing sodium to flow into the cells, which is a process called inactivation. But this inactivated state is different from when the channel is closed, or open for that matter. which are the two states that most other channels have.
The voltage-gated sodium channel though is unique in that it has what's known as the inactivation gate, which blocks sodium influx shortly after depolarization. and stays in this state until the cell repolarizes and the channel enters the closed state again, and the inactivation gate stops blocking influx. Even though that inactivation gate's not blocking it anymore, the channel is still closed, so no sodium enters the cell in this state. The middle open state is therefore the only state where sodium gets let into the cell through the channel, and this is a very short window of time. Now, in addition to these sodium voltage gated We've also got potassium voltage gated channels, which are slow to respond and don't open until the sodium channels have already opened and become inactivated.
The result of this is that after that initial sodium rush into the cell, potassium flows out of the cell down its own electrochemical gradient, removing some positive charge and blunting the effect of the sodium depolarization. These potassium channels don't have a separate inactivation gate, and therefore they stay open for slightly longer. which means that there's a period of time when there's net movement of positive ions out of the cell, which causes the membrane potential to become more negative, or repolarize. During this repolarization phase, the cell also relies on the sodium-potassium pump, which is an active transporter that moves three sodium ions out of the cell and two potassium ions into the cell.
It's during this repolarization phase that the cell is in its absolute refractory period, Since the sodium channels are inactivated and won't respond to any amount of stimuli, this absolute refractory period keeps the action potentials from happening too close together in time and also keeps the action potential moving in one direction. The combined efforts of this pump and the extended opening of the potassium channels result in a small period of overcorrection where the neuron becomes hyperpolarized relative to the resting potential. During this time, the sodium channels go back to their initial closed state, and for a short period the potassium channels stay open. At this point we're in the relative refractory period, since the sodium channels are closed but they can be activated. Although because the potassium channels are still open and we're in a hyperpolarized state, it takes a stronger stimulus to do so.
Finally, as the potassium channels close, the neuron returns to its resting membrane potential. Alright, as a quick graphical recap of this whole process, with membrane potential on the y and time on the x. First we start at the resting membrane potential of around negative 65 mV, and voltage gated sodium and potassium channels are closed. We then receive EPSPs enough to hit threshold at about negative 55 mV, causing voltage gated sodium channels to open and we reach a peak of about positive 40 mV, at which point the sodium channels become inactivated. and we're in the absolute refractory period.
Voltage-gated potassium channels then open, and along with the sodium-potassium pump, start to repolarize the cell, so much so that it overshoots and hyperpolarizes the cell. Next the sodium channels enter their closed resting state, while at the same time potassium channels start to close, meaning that we're in the relative refractory period, until finally they all close and we get to our resting membrane potential once again. Alright, so this process of positive sodium ions moving in and depolarizing the cell transmits the electrical signal down the length of the axon. Great.
But really this process isn't that fast. So that's where the fatty myelin comes in, which comes from glial cells like Schwann cells or oligodendrocytes. These myelinated areas don't have voltage-gated ion channels spanning the membrane, so ions can't simply flow into the cell. That only happens in the spots between the myelin.
called nodes of Ranvier. So instead of propagating via channels, the charge essentially jumps from one node to the next. That said though, jumps isn't really the right term, and these ions aren't just diffusing down the length of the myelin to the other side, that'd be way too slow. What actually happens is more like the sodium ions rush in and bump other positive sodium ions already inside the cell, which bumps other ones, and so on until this wave of positivity reaches the next node. The charge moving in this way down the myelinated areas moves really fast and is called saltatory conduction, which makes it look like the action potential jumps from one node to the next.
Alright, as an extremely quick recap, neuron action potentials happen when dendrites receive enough EPSPs to open voltage-gated sodium channels, which causes rapid depolarization of the neuronal membrane and propagation of an electrical charge from node to node down the length of the axon. You can help support us by donating on Patreon, or subscribing to our channel, or telling your friends about us on social media.